Monitoring of antigen-specific CD8 T cells in patients with type 1 diabetes treated with antiCD3 monoclonal antibodies

被引:34
作者
Cernea, Simonal [1 ]
Herold, Kevan C. [1 ]
机构
[1] Yale Univ, Dept Immunobiol, New Haven, CT 06520 USA
关键词
Type; 1; diabetes; CD8 T cells; Tetramer; AntiCD3 monoclonal antibody; CLASS-II TETRAMERS; ANTI-CD3; MAB; EFFECTOR FUNCTIONS; VIRUS-INFECTION; SINGLE COURSE; RESPONSES; ONSET; INSULIN; MEMORY; MICE;
D O I
10.1016/j.clim.2009.09.005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The way in which anti-CD3 monoclonal antibodies (mAbs) modify human immune responses in type 1 diabetes (T1DM) is not known. We prepared a panel of Class 1 HLA-A2.1 tetramers with peptides from diabetes-associated antigens and studied the frequency and phenotype of the cells in patients with T1DM and blood donors and in patients treated with anti-CD3 mAb (Teplizumab). More patients with T1DM showed positive staining for at least 1 tetramer using frozen and fresh samples (p < 0.05). Three months following treatment with anti-CD3 mAb, the proportion of GAD65- and InsB-peptide reactive CD8+ T cells increased (p < 0.05). The phenotype of these cells was modulated from naive to effector memoryRA+. We concludethat Class 1 MHC tetramers can identify antigen specific CD8+ T cells in patients with T1DM. The frequency of certain specificities increases after treatment with anti-CD3 mAb. Their modulated phenotype may have functional consequences for their pathogenicity. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:121 / 129
页数:9
相关论文
共 44 条
[41]   Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies [J].
Verge, CF ;
Gianani, R ;
Kawasaki, E ;
Yu, LP ;
Pietropaolo, M ;
Jackson, RA ;
Chase, HP ;
Eisenbarth, GS .
DIABETES, 1996, 45 (07) :926-933
[42]   The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes [J].
Wenzlau, Janet M. ;
Juhl, Kirstine ;
Yu, Liping ;
Moua, Ong ;
Sarkar, Suparna A. ;
Gottlieb, Peter ;
Rewers, Marian ;
Eisenbarth, George S. ;
Jensen, Jan ;
Davidson, Howard W. ;
Hutton, John C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (43) :17040-17045
[43]   Humanized, nonmitogenic OKT3 antibody, huOKT3γ(Ala-Ala):: Initial clinical experience [J].
Woodle, ES ;
Bluestone, JA ;
Zivin, RA ;
Jolliffe, LK ;
Auger, J ;
Xu, D ;
Thistlethwaite, JR .
TRANSPLANTATION PROCEEDINGS, 1998, 30 (04) :1369-1370
[44]   In vitro characterization of five humanized OKT3 effector function variant antibodies [J].
Xu, DL ;
Alegre, ML ;
Varga, SS ;
Rothermel, AL ;
Collins, AM ;
Pulito, VL ;
Hanna, LS ;
Dolan, KP ;
Parren, PWHI ;
Bluestone, JA ;
Jolliffe, LK ;
Zivin, RA .
CELLULAR IMMUNOLOGY, 2000, 200 (01) :16-26